3D cell clusters improve diabetes drug testing
Testing diabetes drugs on flat cell layers in a dish is fast, but it barely resembles what happens inside the body. Researchers have developed a scalable 3D model of pancreatic islet cells to close that gap.
The pancreas contains clusters of cells responsible for producing insulin. These clusters, known as islets of Langerhans, contain beta cells that release insulin in response to rising blood sugar. In type 2 diabetes, those beta cells malfunction. Testing new drugs on flat, two-dimensional beta cell cultures has long been standard practice, but such cultures lack the spatial structure and cell-to-cell communication present in real islets.
The researchers, publishing in eLife, developed a platform that generates nineteen uniformly shaped spherical cell clusters (spheroids) in each well of a standard 96-well plate, using mouse beta cells and a polyethylene glycol-based hydrogel. The consistent size and positioning of the spheroids enabled simultaneous real-time imaging of up to 1,824 clusters at once.
What the spheroids reveal
Using this system, the team measured calcium signals inside the cells: calcium oscillations are an intermediate step in the process by which beta cells release insulin. Higher glucose concentrations produced higher oscillation frequencies, which correlated with greater insulin secretion. That relationship also proved sensitive to compounds that block or activate known ion channels in beta cells.
A notable finding involved the neurosteroid pregnenolone sulfate, which activates the TRPM3 ion channel. In the spheroids, it increased the frequency of calcium oscillations and enhanced insulin release. A blocker of the same channel suppressed those effects. This provides a concrete example of how the platform can identify compounds that modulate insulin secretion.
Scalable model for drug screening
The relevance to aging is indirect but real: insulin resistance and reduced beta cell function increase with age. Better models for testing diabetes drugs can accelerate the development of treatments that remain effective at older ages. The platform is currently limited to mouse cells and requires validation in human cells before clinical conclusions can be drawn.
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